Predictive value of testing for maternal plasma cell-free fetal DNA in fetal growth restriction

Aim. To investigate the relationship between changes in cell-free fetal DNA (cfDNA) level and placental morphology in fetal growth restriction (FGR) and determine its predictive value. Materials and methods. The study included 93 pregnant women, including 48 pregnant women with FGR (group I, 23 with early and 25 with late-onset FGR), and 45 women with uncomplicated pregnancy (group II, comparison group). The analysis included clinical and anamnestic data, the course of pregnancy and delivery, and the fetus and newborn health status. Maternal plasma cfDNA was measured by real-time polymerase chain reaction. Placentas were examined using the terminal deoxyuridine end-labeling (TUNEL) technique and immunofluorescence analysis. Results. The level of cfDNA in early-onset FGR [89.03 (44.52; 178.32) GE/ml] was statistically significantly lower than in the late FGR and the comparison group [244.14 (145.23; 422.47) and 211.05 (133.64; 567.81) GE/ml], (p <0.001). ROC analysis showed that testing for maternal plasma cfDNA at the threshold of119.11 GE/ml had high sensitivity (73.1%) and specificity (79.3%) (AUC = 0.81, 95% cI 0.63-0.98) for detecting early FGR and predict the likelihood of newborn complications. The f indings on placental architectonics included the predominance of fibrosis processes and the formation of extensive fibrinoid zones. This observation explains the decrease in cfDNA and impaired placental perfusion leading to FGR. It confirms the relationship between low cfDNA levels and the risk of having children with stunted growth. Also, there was strong positive correlations between the cfDNA level, body weight (r = 0.72; p <0.001) and length (r = 0.71; p <0.001) of newborns in cases of early-onset FGR. Conclusion. The study identified the diagnostic accuracy of cfDNA for differentiating early from late-onset FGR. The findings suggest that early and late-onset FGR have different underlying mechanisms. Testing for cfDNA allows for predicting the risk of having children with low body weight and height. The findings on the high diagnostic accuracy of cfDNA in detecting the early FGR suggest the prospects of using cfDNA as a predictive marker.

TUNEL, fetal growth restriction, extracellular fetal DNA, blood plasma, placenta, TUNEL